KURSK STATE MEDICAL UNIVERSITY

Student: Guilherme L. Paschoalini

Group: 29 – 2ºyear

METABOLISM IN DIFFERENT ORGANS

KURSK - 2014

MACRONUTRIENTS• Organic compounds that yield Energy• Classified as: Carbohydrates; Fats/Lipids; Proteins

Major Metabolic Pathways: Glycolysis

GluconeogenesisGlycogen MetabolismFatty Acid Metabolism

Citric Acid CycleOxidative Phosphorylation

Amino Acid Metabolism

Only the liver can carry out all of the reaction the major pathways.

Position of metabolic pathways

Metabolic Fate of Glucose• Glucose: The intracellular form of glucose is glucose-6-phosphate.• Only liver cells have the enzyme glucose-6-phosphatase that

dephosphorylates G-6-P and releases glucose into the blood for use by other tissues

• G-6-P can be oxidized for energy in the form of ATP and NADH• G-6-P can be converted to acetyl CoA and then fat.• Excess G-6-P is stored away as glycogen.• G-6-P can be shunted into the pentose phosphate pathway to generate

NADPH and ribose-5-phosphate

Metabolic Fate of Fatty Acids• Fatty acids are oxidized to acetyl CoA for energy production in the form

of NADH.• Fatty acids can be converted to ketone bodies. KB can be used as fuel

in extrahepatic tissues.• Fatty acids are used for the biosynthesis of bioactive molecules such as

arachidonic acid and eicosanoids.• Cholesterol, steroids and steroid hormones are all derived from fatty

acids.• Excess fatty acids are stored away as triglycerides in adipose tissue.

Metabolic Fate of Amino Acids• Amino acids are used for the synthesis of enzymes, transporters and

other physiologically significant proteins.• Amino acid N is required for synthesis of the cell’s genetic information

(synthesis of nitrogenous bases).• Several biologically active molecules such as neurotransmitters.• Amino acids are precursors of several hormones (peptide hormones

like insulin and glucagon and Amine hormones such as catecholamines).

• Aminoacids can be catabolized to acetyl CoA, pyruvate or intermediates of the TCA cycle for complete oxidation

Central Themes of Metabolic Pathways• Acetyl CoA is a common intermediate of all metabolic pathways. It

interconnects glucose, fatty acid and amino acid metabolism.• Oxidation of dietary fuel leads to the capture of energy in the form of

ATP and NADH / FADH2.• NADH / FADH2 transfer their electrons to O2 via the electron

transport chain. The energy released is used to synthesize ATP.• Biosynthetic and degradative pathways are distinct and coordinately

regulated.

BRAIN• Glucose is virtually the sole fuel for the human brain, except

during prolonged starvation. The brain lacks fuel stores and hence requires a continuous supply of glucose.

• It consumes about 120 g daily, which corresponds to an energy input of about 420 kcal 

• Much of the energy, estimates suggest from 60% to 70%, is used to power transport mechanisms that maintain the Na+-K+ membrane potential required for the transmission of the nerve impulses.

• Overall, glucose metabolism remains unchanged during mental activity, although local increases are detected when a subject performs certain tasks.

• The brain cannot store glycogen, it must receive a constant supply of glucose through the blood. Brain cells have a glucose transporter, GLUT3,with a low Km for glucose.

• Fatty acids do not serve as fuel for the brain, because they are bound to albumin in plasma and so do not traverse the blood-brain barrier. In starvation, ketone bodies generated by the liver partly replace glucose as fuel for the brain.

MUSCLE• The major fuels for muscle are glucose, fatty acids, and

ketone bodies. Muscle differs from the brain in having a large store of glycogen (1200 kcal, or 5000 kJ). In fact, about three-fourths of all the glycogen in the body is stored in muscle

• This glycogen is readily converted into glucose 6-phosphate for use within muscle cells. Muscle, like the brain, lacks glucose 6-phosphatase, and so it does not export glucose. Rather, muscle retains glucose, its preferred fuel for bursts of activity.

• In actively contracting skeletal muscle, the rate of glycolysis far exceeds that of the citric acid cycle, and much of the pyruvate formed is reduced to lactate, some of which flows to the liver, where it is converted into glucose

• A large amount of alanine is formed in active muscle by the transamination of pyruvate. Alanine, like lactate, can be converted into glucose by the liver. Muscle can absorb and transaminate branched-chain amino acids; however, it cannot form urea.

• Unlike skeletal muscle, heart muscle functions almost exclusively aerobically, as evidenced by the density of mitochondria in heart muscle. Moreover, the heart has virtually no glycogen reserves. Fatty acids are the heart's main source of fuel, although ketone bodies as well as lactate can serve as fuel for heart muscle. In fact, heart muscle consumes acetoacetate in preference to glucose.

ADIPOSE TISSUE• The triacylglycerols stored in adipose tissue are an enormous

reservoir of metabolic fuel• Adipose tissue is specialized for the esterification of fatty acids

and for their release from triacylglycerols. In human beings, the liver is the major site of fatty acid synthesis.

• Recall that these fatty acids are esterified in the liver to glycerol phosphate to form triacylglycerol and are transported to the adipose tissue in lipoprotein particles, such as very low density lipoproteins Triacylglycerols are not taken up by adipocytes; rather, they are first hydrolyzed by an extracellular lipoprotein lipase for uptake. This lipase is stimulated by processes initiated by insulin.

• Adipose cells need glucose for the synthesis of triacylglycerols• Triacylglycerols are hydrolyzed to fatty acids and glycerol by

intracellular lipases. • Glycerol derived from their hydrolysis is exported to the liver.

Most of the fatty acids formed on hydrolysis are reesterified if glycerol 3-phosphate is abundant.

• Glucose level inside adipose cells is a major factor in determining whether fatty acids are released into the blood.

KIDNEY• The major purpose of the kidney is to produce urine, which

serves as a vehicle for excreting metabolic waste products and for maintaining the osmolarity of the body fluids. The blood plasma is filtered nearly 60 times each day in the renal tubules. 

• During starvation, the kidney becomes an important site of gluconeogenesis and may contribute as much as half of the blood glucose. The kidneys are a minor site of gluconeogenesis(liver is the major site).

LIVER• The metabolic activities of the liver are essential for

providing fuel to the brain, muscle, and other peripheral organs

•  The liver removes two-thirds of the glucose from the blood and all of the remaining monosaccharides. Some glucose is left in the blood for use by other tissues. The absorbed glucose is converted into glucose 6-phosphate by hexokinase and the liver-specific glucokinase

• Much of the glucose 6-phosphate is converted into glycogen. Excess glucose 6-phosphate is metabolized to acetyl CoA, which is used to form fatty acids, cholesterol, and bile salts.

• The liver can produce glucose for release into the blood by breaking down its store of glycogen and by carrying out gluconeogenesis.

• The main precursors for gluconeogenesis are lactate and alanine from muscle, glycerol from adipose tissue, and glucogenic amino acids from the diet.

• The liver cannot efficiently use glucose or ketone bodies as fuel. It prefers fatty acids and α-keto acids as a source of energy for its activities.

• Hepatic lipid metabolism:When fatty acids are in excess, they are exported to the adipose tissue for storage as TG. TG are transported as VLDL particles assembled from newly synthesized or dietary fatty acids.

• In the fasting state, liver converts fatty acids into ketone bodies.

REFERENCES• Biochemistry, 5th edition - Jeremy M Berg, John L

Tymoczko, and Lubert Stryer• Lehninger Principles of Biochemistry - by  Albert L.

Lehninger• Biochemistry - Jeremy M. Berg• Lippincott's Illustrated Reviews: Biochemistry